ps418

I too could argue that it shows a common creator.

I've always wondered, what testable predictions can be derived from the hypothesis of a common creator, and how are they derived? What observational data would be inconsistent with the 'common creator hypothesis'? Any thoughts on this?

CodeMason

That ebook is brilliant scigirl, many thanks for the link.

tronvillain

davidH:
No, the introns are replicated right along with exons. They are only spliced out of the RNA transcripts after transcription.

It could, if the change was in the short consensus sequences at the ends of the intron, or possibly if the change was in some other element. Apparently such mutations have been <a href="http://opbs.okstate.edu/~melcher/MG/MGW2/MG2315.html" target="_blank">observed</a>.

tronvillain

davidH
As far as I know, they're still working on this question - you have reached the edge of the known.

Valentine Pontifex

It should be noted that that number is for one copy of each of the 22 non-sexual chromosomes plus the x chromosome and the y chromosome. A real living human cell is generally diploid. Most human cells have about 6 billion base pairs.

CodeMason

The large majority of introns are worthless, hence the term "junk", but I'm sure many serve a purpose. For example, as others have shown in this thread, a mechanism to contain the effects of a frame shift mutation to a single gene. And some have been shown to have actually useful information for something or other (what that is exactly, is as of yet unknown.)

Yellow3

A friend of mine who works for a bioengineering company recently told me the worth of introns. Her company had been researching gene-therapy techniques for one of the types of hemophilia; however, the gene for the blood-clotting factor that is missing in these individuals is (relatively) huge compared to the space inside the viral vector. To be able to stuff all the useful information in, they tried removing the introns and tested the new vector.

The all-exon gene didn't work.

They have no idea what's wrong or what the mechanism is, but when the introns are spliced out, the exons will not function properly when reintroduced to a eukaryotic host. I think they're running research to figure out what exactly this 'junk' DNA is doing. And, presumably, scrambling to find a bigger vector!

- Jen

davidH

Yeah, thanks a lot for the web address of the online text book! It helps a lot and goes into good detail.

Ok, so there does seem to be something about the introns that makes them far more than just junk. What that is, is at the moment unkown. I came across this in my reading and it again seems to show that introns are important. I think I'll put it up here incase you haven't read it before.


Taken from Biology principles and processes, Michael Roberts, Michael Reiss, Grace Monger.

So this at least does show us that the introns do serve a useful purpose?
I find it quite incredable that the alteration of only 1 base in the intron (in this case) could cause so many abnormalities and serious problems.

So from what this passage says and also what was writen by Yellow3 above, can I assume that the introns aren't useless junk but play a vital role in something?

If this is the case as the evidience at the moment seems to suggest, can I also assume that mutations in the intron are more likely cause serious problems - because the evidience doesn't point at it being useless DNA?

I have another question for those that know about all this stuff.
Say we have the following code;

AGTUAUTATGUUAGTTUAGAUTGTAUGUATGTUAATGUT

The bits in bold are the exons and the middle bit is the intron.
The enzyme is specific to the base pairs right? So say it cuts at T and its base pair, and also U and its base pair (assuming it cuts vertically).
So causing that whole intron to be removed.What would happen if an addition were caused before the first T? How would that affect the whole process that comes next?

According to the passage above, how could a thymine entered at 19 bases from the junction of the intron and the exon cause the mRNA to be improperly edited and spliced before its exported from the nucleus?

(Note; I think the enzymes remove the intron from the mRNA?)

scigirl

You're welcome.

I'm not exactly sure why you are trying to prove that introns are "useful." In the evo/cre debate, this fact is irrelevant anyway.

Evolutionary biologists claim that they are evidence for evolution--irrespective of their use. It's the pattern of intron sequences that correlate with evolutionary trees that is important here. For instance, we better have more similar introns to chimps than dogs if evolution is correct (we do). Also, since introns can mutate quite a bit and not screw us up, they can provide helpful phlogenetic information.

In some cases, introns are worthless, in others perhaps they are helpful (contain an enhancer or an alternative translation start site) and in still other cases, they could evolve a new and novel function in the future. There are certainly genes where alternative splicing plays an important regulatory role.

What is your point exactly?

I think this is faulty logic. Let's say I hold a gun to your head, then I throw the gun away and claim I saved your life. Why hold the gun up to your head if I wanted you to live in the first place? The whole system of introns and exons smacks of evolutionary proof! Why not just make separate genes for everything if you were going to "create" all the genes separately?

If I was going to make a hemoglobin gene, I wouldn't put any introns in the DNA at all! If the gene was intact in the DNA and led directly to mRNA (no intron spicing needed) than this disease would not occur.
It does seem pretty crazy, that is until you take biochemistry. Sickle-cell anemia is one example--it is really easy to understand how this occurs from just one base pair substitution when you learn about tertiary structure of polypeptides.

No, mutations in the exon are still going to affect the gene way more, obviously. But if the mutation occurs in the intron splice site (which of course serves the useful purpose of removing the useless information).

First of all, you will never see Ts and Us in the same sequence. DNA contains A, C, T, and G. RNA contains A, C, U, and G.

It does cut vertically--it's not a sticky end cutter.

This would be a frameshift mutation because it would alter the coding sequence. Remember, introns are the "junk," exons are the good stuff.

If it occured anywhere in the intron {other than the signal to cut sequence), than it would produce no effects.

Because the spliceosome recognizes certain bases in the intron to cut out the intron. These bases are not necessarily the bases at the "ends."
Yes.

This issue is fairly complex by the way, and scientists are still trying to figure out how to predict intron-exon sequences from looking at the raw DNA. It does vary from species to species.

<a href="http://www.swbic.org/education/comp-bio/intron.htm" target="_blank">Here's</a> a site that goes into more details.

scigirl

Edited to add: The splicing machinery reconizes certain bases in both the intron and the exon--very strange indeed!

[ January 21, 2002: Message edited by: scigirl ]</p>

theyeti

I think this has already been answered, but I'll do it again anyway. Not all introns require enzymes for their removal. Group II introns, and I think some others, are self-splicing; that is that they have the catalytic ability to remove themselves without outside help. For these introns, much of their internal sequence is necessary for self-splicing, so that mutations might interupt their ability to remove themselves. However, an insertion/deletion will not have the dramatic frameshift properties that it can have with an exon.

Other introns are known as spliceosomal, which means that they require a protein/RNA complex known as the spliceosome for their removal. There is evidence that splicesomal introns, and indeed, the splceosome itself, evolved from group II self-splicing introns. As for spliceosomal introns, their internal sequences are much less important. They do need consensus sequences for the recognition of the spliceosome -- for instance, all of them begin with GU and end with AG (or mabey that's the exons -- I forget). But the vast majority of their internal sequences are indeed "junk". This is why humans can have much, much longer introns than, say, Fugu (puffer fish) even though the intron/exon structure is the same for homologous genes.

So an insertion/deletion in spliceosomal introns is unlikely to have any effect. If there is an effect, it will likely cause whole or part of the intron to become part of the mature transcript, and therefor add a bunch of extaneous amino acids in the middle of the protein. There is also a chance that it could cause a frameshift. If it does add these extra amino acids, the severity of the mutation depends largely on the size of the intron. In humans, since the introns are so much larger than the exons, it's likely to have a major effect. But in other organisms, where the introns are not as large, it may make no difference. It could even be helpful by adding a spacer between functional protein domains. In fact, there is strong evidence that a few recently evolved (&lt;10 Mya) novel genes have had intronic sequences stuck into their coding sequences.

That's a very good question. There are probably two reasons why introns are maintained. The first is that they're useful (probably an absolute necessity) for alternative splicing of RNA transcripts. What this means is that the exons can be spliced together in different ways, for example, by skipping one of them. This means that a single gene can produce many different protein products, often times in a tissue specific manner. It is thought that the ability to add new proteins via alternative splicing is a major contributor to the evolution of increased coding complexity. A recent Nature Genetics article (vol. 30 no.1 jan 2002 p. 29) estimates that as many as 50% of human genes can and do alternatively splice, and that this is common among other eukaryotes.

The second reason is what's know as exon-shuffling. Exon-shuffling was first proposed by Walter Gilbert in a 1979 Nature article -- the very same one where he coined the term "intron"! Briefly, exon-shuffling is the idea that during recombination, different exons can be mixed and matched with one another to create new, novel proteins. One thing that introns do is that they greatly increase the size of genes, so that each individual gene is far more likely to recombine. (This by itself will help increase the spread of good mutations). Sometimes recombination occurs in such a way as to make one of the daughter chromosomes have exta DNA, and through a variety of methods, a given exon can be duplicated, inverted, or placed in another gene. Since exons tend strongly to correlate to functional protein modules, this allows for the evolution of novel, functional proteins from existing pieces. Exon-shuffling almost certainly plays a major role in the evolution of increased genetic "information".

As for the origin of introns, they probably originated from retrotransposons. Retrotransposons are bits of DNA that get transcribed into RNA, and then reverse-transcribe themselves into DNA so that they can get inserted into other places in the genome. A fairly large percentage of our own DNA is made up of these sequences. They truly appear to be "selfish" DNA, existing primarily if not exclusivly for the purpose of their own propagation. It is more useful to think of them as retroviruses that lack protein envelopes for contagiousness. In fact, some retrotransposons have other retrotransposons inside of them, like a flea within a flea. Group II introns probably evolved from retrotransposons a very long time ago. It is advantageous for the intron to remove itself from the transcipts of any coding sequences that it inserts into so that the phenotype of the host organism is not terribly altered. And from there, spliceosomal introns probably evolved from group II introns, as per above.

There is some pretty serious debate about whether introns are ancient and were present since the beginning of life, or are relatively recent additions. If you're really interested you can see a thread on "introns-early vs. introns-late" in the archives from last quarter, but it gets a bit technical. The general consensus is that some introns probably are ancient, but that the vast majority of them have been inserted de novo into genomes throughout evolution. In fact, de novo insertion has been observed, and the phylogenetic evidence strongly favors it. Quickly reproducing organisms for whom DNA replication is a high metabolic demand tend to have few or no introns. In all likelihood, introns have been continuously inserting themselves into genomes throughout time, but fast replicators have a strong selective pressure to get rid of them. Larger organisms for whom DNA replication is an insignificant metabolic concern, such as ourselves, have little or no selective pressure to remove them. (Most of our energy is used for things like muscle contraction and brain activity.) Thus, they have tended to accumulate to almost absurd proportions.

Nuts. A common creator does not predict the similarity of intron/exon structure at all, and it certainly doesn't predict the similarity of intronic sequences between organisms of close morphology.

theyeti